Analysis of field-induced transmembrane potential responses of single cardiac cells in terms of active and passive components

Field-induced transmembrane potential (V_m) responses of cardiac cells have complex spatiotemporal variation. We show that these responses can be decomposed into simpler components that facilitate their understanding. Enzymatically isolated guinea pig cardiac cells were stained with ~50 μM voltage sensitive dye di-8-ANEPPS, and stimulated along their longitudinal axes using a pair of S1 (5 ms) and S2 (10 ms) uniform field pulses (S1-S2=20 ms). The V_m responses recorded using a multisite optical mapping system were decomposed into a differential-mode component V_md and a common mode component (V_mc). The V_md varies linearly along the cell length, and describes the passive component of the field responses. The V_mc is uniform along the cell length, and describes the active component. The V_mc arises from an imbalance in membrane currents along the cell length, and is depolarizing at rest and hyperpolarizing during the plateau. It has been shown previously that a model cell with dynamic Luo-Rudy) membrane currents fails to reproduce the hyperpolarizing V_m responses during the plateau, and a hypothetical outwardly rectifying current I _a has been proposed to resolve the discrepancy. However, the true ion channel basis of I_a has not been resolved. Using pharmacological interventions we dissect the membrane currents involved during the plateau responses, and suggest that the sustained plateau current (I_kp) is most likely the ion channel correlate of I _a